X-154437141-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000630693.2(GDI1):c.-114C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 685,765 control chromosomes in the GnomAD database, including 2 homozygotes. There are 176 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (1 hom., 23 hem., cov: 22)
  • Exomes 𝑓: 0.00098 (1 hom. 153 hem.)
• Consequence: GDI1 ENST00000630693.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510

Genes affected

GDI1 (HGNC:4226): (GDP dissociation inhibitor 1) GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI1 is expressed primarily in neural and sensory tissues. Mutations in GDI1 have been linked to X-linked nonspecific cognitive disability. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154437141-C-T is Benign according to our data. Variant chrX-154437141-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDI1	NM_001493.3			upstream_gene_variant		ENST00000447750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDI1	ENST00000447750.7			upstream_gene_variant		1	NM_001493.3	P1

Frequencies

GnomAD3 genomes AF: 0.000853 AC: 94 AN: 110251 Hom.: 1 Cov.: 22 AF XY: 0.000703 AC XY: 23 AN XY: 32739

Gnomad AFR AF: 0.000197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000566

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000982 AC: 565 AN: 575473 Hom.: 1 Cov.: 9 AF XY: 0.00100 AC XY: 153 AN XY: 152261

Gnomad4 AFR exome AF: 0.0000763

Gnomad4 AMR exome AF: 0.0000937

Gnomad4 ASJ exome AF: 0.0000796

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000281

Gnomad4 FIN exome AF: 0.000893

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.000468

GnomAD4 genome AF: 0.000852 AC: 94 AN: 110292 Hom.: 1 Cov.: 22 AF XY: 0.000701 AC XY: 23 AN XY: 32790

Gnomad4 AFR AF: 0.000196

Gnomad4 AMR AF: 0.000565

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000173

Gnomad4 NFE AF: 0.00155

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00124 Hom.: 7

Bravo AF: 0.000759

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

GDI1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.6
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1414341641; hg19: chrX-153665487;